That diverse cast is a great selling point for distributor Warner Bros., which opens “Cloud Atlas” in U.S. theaters Oct. 26. So, too, is the filmmaking team: American siblings Lana and Andy Wachowski, creators of “The Matrix” films, who wrote the screenplay and directed “Cloud Atlas” with German filmmaker Tom Tykwer (“Run Lola Run”).

The fact that the film is adapted from a best-selling novel also should help its audience appeal. Yet considering that “Cloud Atlas” author David Mitchell himself once felt the novel was unfilmable, fans of the book may have serious doubts about handing over their cash and spending nearly three hours in a theater to digest Hollywood’s version.

It’s such a tough sell that even the notoriously media-shy Wachowskis, who had a no-press clause on earlier films, are out there eagerly hawking “Cloud Atlas.”

“It’s dear to us, and that’s definitely part of it. Our partnership with Tom, our marriage with Tom, that’s definitely a part of it. Tom engages with the press and has shown us, taught us some tricks that have made it a little easier for us to get back involved,” said Mr. Wachowski in an interview alongside his sister, who is transgender and changed her name from Larry to Lana, and their longtime pal Mr. Tykwer.

With mixed but generally appreciative early reviews — some critics reveling in its audacity and even detractors admiring its ambition — “Cloud Atlas” already is an artistic success simply by existing, given its unlikely path to the screen.

The Wachowskis discovered the book when Natalie Portman was reading “Cloud Atlas” on the set of their 2006 thriller “V for Vendetta.” The siblings recommended the novel to Mr. Tykwer, and the three spent years overcoming creative and commercial obstacles to adapt it for film.

The $100 million budget was pieced together from a variety of international financiers and distributors; Warner Bros. acquired U.S. rights but declined to finance the film, despite the studio’s success with the Wachowskis’ “Matrix” trilogy.

Then there were the challenges of condensing dozens of key characters in six stories that span the globe and sprawl across 500 years as reincarnated souls progressing through the ages.

“The book seemed almost like a revolutionary act in and of itself,” Ms. Wachowski said. “David has said since that they did have trouble with, do you put it in science fiction, do you put it in drama? Where do you put it on the shelf in the bookstore?”

The way they cracked the code was, in a word Mr. Mitchell tosses about repeatedly, ingenious. The same actors would play characters in different periods, sometimes switching race and gender, as each soul moves upward, downward or sideways on the karmic plane.

“The book is unfilmable, but they haven’t quite adapted the book,” Mr. Mitchell said. “They sort of disassembled the book and reassembled it in the form of a filmable film by having actors recurring, and implying therefore it’s the same soul on this sort of ethical journey — or, no pun intended, a matrix of ethical journeys.”

So Mr. Hanks is a rapacious doctor in 1849, a murderous thug with artistic pretensions in 2012, a cowardly goatherd inching toward enlightenment in the 24th century. Miss Berry is a white Jewish adulteress in the 1930s, a gutsy journalist in the 1970s, an Asian medical man in the 22nd century and part of an elite race of survivors in the 24th.

The film’s prologue is an assault of images and characters introducing six time periods and stories, with “Cloud Atlas” then settling into a kaleidoscope that shifts from era to era, deconstructing the chronological structure of the half-dozen narratives in Mr. Mitchell’s novel.

“There are going to be people out there who are going to say, ‘Who do they think they are to make this movie like this?’ That’s been the case with every great film. They said the same thing about ‘The Cabinet of Dr. Caligari’ in the silent days,” Mr. Hanks said. “I think every audience is yearning to be surprised.

“I am bored when I walk into the theater expecting A, B and C, and a movie delivers A, B and C. I want to see something brand new that I never anticipated coming a hundred million miles away. And my God, that happens before the words ‘Cloud Atlas’ appear up on the screen on this one.”

With the Wachowskis directing the 1849 segment and the two futuristic ones and Mr. Tykwer overseeing the 1930s, 1970s and contemporary stories, “Cloud Atlas” could have been a schizophrenic mess.

The actors shuttled from sets in Scotland, Germany and Spain, changing costumes, characters and directors from day to day.

“I was most frightened about that, thinking, ‘Oh God, how’s it going to be with three directors? Am I going to be confused? Who do I listen to, and what’s it going to be like?’ But it was none of that,” Miss Berry said. “They spent so many years talking about it, honing their ideas and figuring it all out, they were very much on the same page.”

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